# Hippocampal Inflammation as a Pathophysiology for Psychosis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $716,456

## Abstract

ABSTRACT:
Schizophrenia and other psychotic disorders are conditions of enormous costs to individuals,
families and to the public. Treatment is often geared to large diagnostic groups, but psychotic
conditions are comprised of a group of disorders that likely vary in their primary pathophysiology
for which personalized treatments must be developed. Traditional DSM based disorders have
not explained this heterogeneity. One possible driver of psychosis across disorders is
hippocampal inflammation, which could be a target for person specific treatment. We have
identified two separate inflammatory processes in schizophrenia using advanced imaging
techniques. This study replicates the hippocampal inflammation finding in psychosis and tests if
these are the source of psychotic symptoms. It furthermore tests the hypothesis that the
inflammation is related to pathology in the gut-brain-axis (GBA) and particular species in the gut
microbiome composition. The components of the GBA include resident microorganisms in the
gut, parasympathetic (vagal) autonomic nervous systems (ANS) connections between the brain
and the gut and circulating immune molecules. This study compares 50 cases, defined as
having six months of chronic psychosis to 25 group mean age and sex matched comparison
subjects without psychiatric disorders. To test the specificity of our results for psychosis we will
also study 25 psychiatric cases without psychosis recruited from the same treatment settings.
Imaging measures to determine hippocampal inflammation that is related to dysmyelination and
inflammation for the microglia are 3 dimensional multivoxel MRSI imaging and diffusion kurtosis
imaging (DKI) respectively. The arms interconnecting the gut to the brain through the vagal
nerve and circulating inflammatory molecules will be examined individually and as an integrated
system with respect to the two inflammation biomarkers. Gut inflammation will be assessed in
stool samples by calprotectin levels, an inflammatory marker, and the genomic composition of
the microbiome will be examined in highly sophisticated analyses. Using computational science
and bioinformatics, this information will be integrated to test the relationship of the GBA to
hippocampal inflammation. This multidisciplinary project brings scientists together from across
the NYU medical center and includes expertise from Mt. Sinai, Columbia University and the
University of Georgia's Medical Schools. Finding a microbiome or gut-brain-axis signature for
hippocampal inflammation in psychotic persons will set the stage for the development of novel
person specific treatments. If particular gut species are identified, future studies will examine
their effects on the phenotype in mouse models for advancing novel treatments for psychosis.

## Key facts

- **NIH application ID:** 10213591
- **Project number:** 5R01MH110418-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** DOLORES MALASPINA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $716,456
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213591

## Citation

> US National Institutes of Health, RePORTER application 10213591, Hippocampal Inflammation as a Pathophysiology for Psychosis (5R01MH110418-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10213591. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*